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Cerebral metabolic effects of CI‐943 (8‐Ethyl‐7,8‐dihydro‐1,3,5‐trimethyl‐1Himidazo[1,2,‐c]pyrazolo[3,4‐e]‐pyrimidine), a potential antipsychotic drug
Author(s) -
Kimes Alane S.,
Raymon Lionel P.,
Meltzer Leonard T.,
Heffner Thomas,
London Edythe D.
Publication year - 1991
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430240103
Subject(s) - antipsychotic , globus pallidus , substantia nigra , pharmacology , dopamine , basal ganglia , medicine , endocrinology , chemistry , central nervous system , schizophrenia (object oriented programming) , dopaminergic , psychiatry
CI‐943 is a novel drug candidate that has antipsychotic‐like activity in a variety of behavioral tests in rodents and primates, but has no affinity for brain dopamine (DA) receptors. In order to obtain information on the neuroanatomical substrates for its behavioral actions, we used the autoradiographic 2‐deoxy‐D‐[1‐ 14 C]‐glucose method to map and quantify the distribution of CI‐943 effects on the regional cerebral metabolic rate(s) for glucose (rCMRglc) in the rat. The effects of CI‐943 (40 mg/kg) were assessed at 10 and at 60 min after the drug was administered intraperitoneally. In the globus pallidus and the substantia nigra pars reticulata, rCMRglc were increased at 60 min following treatment, and in the lateral habenula, rCMRglc was increased at 10 and 60 min after treatment. In contrast, the predominant effect of CI‐943 in other areas (e.g., most cortical, several thalamic, basal ganglia, limbic, and midbrain areas) was to reduce rCMRglc. The metabolic pattern produced by CI‐943 was unique and consistent with previous findings that CI‐943 resembles other antipsychotic drugs in behavioral tests but differs from those agents in tests prodictive of extrapyramidal dysfunction.